The chimpanzee GH locus: composition, organization, and evolution

Abstract

In most mammals the growth hormone (GH) locus comprises a single gene expressed primarily in the anterior pituitary gland. However, in higher primates multiple duplications of the GH gene gave rise to a complex locus containing several genes. In man this locus comprises 5 genes including GH-N (expressed in pituitary) and four genes expressed in the placenta, but in other species the number and organization of these genes varies. The situation in chimpanzee has been unclear, with suggestions of up to seven GH-like genes. We have re-examined the GH locus in chimpanzee and have deduced the complete sequence. The locus includes five genes apparently organized in a similar fashion to those in human, with two of these genes encoding GH-like proteins, and three encoding chorionic somatomammotropins/placental lactogens (CSHs/PLs). There are notable differences between the human and chimpanzee loci with regard to the expressed proteins, gene regulation and gene conversion events. In particular, one human gene (hCSH-L) has changed substantially since the chimpanzee/human split, potentially becoming a pseudogene, while the corresponding chimpanzee gene (CSH-A1) has been conserved, giving a product almost identical to the adjacent CSH-A2.Chimpanzee appears to produce two CSHs, with potentially differing biological properties, whereas human produces a single CSH. The pattern of gene conversion in human has been quite different from that in chimpanzee. The region around the GH-N gene in chimpanzee is remarkable polymorphic, unlike the corresponding region in human. The results shed new light on the complex evolution of the GH-locus in higher primates.

Developmental programming of growth: Genetic variant in GH2 gene encoding placental growth hormone contributes to adult height determination

“…In Europe, there appears to be a West-East gradient of the A-allele frequency, from 30% in Central-Europe to 20% at the Volga-Ural region bordering Europe and Asia. In human-chimpanzee comparison, GH2 is the most conserved gene in the GH/CSH cluster and so far only chromosomes with C-allele at the position c.171 + 50C > A have been described [26]. Also, all the rest of the highly homologous genes in the h GH/CSH cluster ( GH1 , CSH1 , CSH2 , CSHL1 ) are monomorphic for the C-nucleotide at this position (Supplemental Fig.…”

Structure and evolution of the gorilla and orangutan growth hormone loci

“…The final assembly of the genomic sequences for the gorilla and orangutan GH loci was achieved using the approach previously described (Wallis 2008;Pérez-Maya et al 2012). Using BLAST and BLAT search methods (Altschul et al 1990;Kent 2002), human GH gene regions were used as query sequences to identify sequences from the WGS trace archive (http://www.ncbi.nlm.nih.gov/Traces).…”

Evolution of Placental Function in Mammals: The Molecular Basis of Gas and Nutrient Transfer, Hormone Secretion, and Immune Responses

“…The GH locus of the chimpanzee (Pan troglodytes) includes genes for GH-N, GH-V, and three PL-like genes (293). One PL-like gene, predicted to be functional, is orthologous to a human pseudogene (293,312).…”

“…The GH locus of the chimpanzee (Pan troglodytes) includes genes for GH-N, GH-V, and three PL-like genes (293). One PL-like gene, predicted to be functional, is orthologous to a human pseudogene (293,312). The genome of lowland gorilla (Gorilla gorilla) has two GH and four PL-like genes, but the duplication within the PL-like cluster is different from that in the chimpanzee (318).…”